Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinocerebellar ataxial 1 (SCA1) is the locus name of autosomal dominant olivopontocerebellar atrophy (OPCA), and is assigned to the short arm of chromosome 6. The tight linkage between SCA1 and D6S89 has recently been reported. In order to examine possible locus heterogeneity, we studied linkage for D6S89 to disease loci in 16 pedigrees of dominant OPCA. D6S89 polymorphism was analysed with PCR amplification of genomic DNA by using specific oligonucleotide primers. Lod scores were computed by LIPED program with the correction of age-dependent penetrance. Homogeneity test was performed by using HOMOG program. Fifteen out of 16 pedigrees were informative to D6S89. Among them, 7 pedigrees showed positive and 8 pedigrees showed negative lod scores throughout all recombination fractions. Homogeneity testing disclosed that approximately 55% of pedigrees are linked to D6S89, and others were not linked. Our results provide evidences that dominant OPCA in Japan are genetically heterogenous. At now, it has been still unknown whether there are any clinico-pathological differences among OPCA genotypes. Based on the alpha-constant from homogeneity testing, we divided our pedigrees into linked-pedigree (SCA1) and nonlinked-pedigrees (nonSCA1). Then, clinical features were compared between these two groups. Hyperactive DTR was more common in SCA1 than nonSCA1 group. On the other hand, hypoactive DTR was more significantly dominated in nonSCA1 than SCA1. Slow saccade and Babinski sign were common in both groups. Although not statistically significant, nystagmus, exteral ophthalmoparesis, mydriasis, ptosis, facio-lingual twitching, and limb spasticity were more frequently observed in SCA1 than nonSCA1. These results indicate that there are possible correlation between disease genotype and phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Linkage study of hereditary olivopontocerebellar atrophy: genetic evidence for locus heterogeneity in Japanese cases]. 162 32

From the linkage study of D6S89, we previously reported that hereditary OPCA in Japan is genetically heterogenous. Two pedigrees, P2 and P35, reported in this report, were not linked to D6S89. In order to examine possible correlation between OPCA genotypes and disease phenotypes, we studied clinically eight cases in these two pedigrees. One autopsied case in pedigree P2 was proven to have marked neuronal degeneration in the inferior olivary nuclei, pontine nuclei, cerebellar cortex, and substantia nigra. Dentate nucleus and oculomotor nuclei were free from neuronal degeneration. Clinical features of those 8 patients were fairly uniform, characterized by cerebellar ataxia, hypoactive DTR, and slow eye movement. Parkinsonism or choreiform movements were observed in one patient, respectively. Pupillary dilatation, twitching of face and tongue, limb amyotrophy were observed in patients of advanced stages. However, these signs were not dominating nor common throughout clinical course. None of our cases showed hyperactive DTR, limb spasticity, or external ophthalmoparesis. On the other hand, these latter signs were popular in SCA1 so far as reviewing the literature. The present study showed that there was possible correlation between genotypes and phenotypes in hereditary OPCA.
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PMID:[Clinical study of gene locus heterogeneity in hereditary olivopontocerebellar atrophy (OPCA)--report of 2 pedigrees affected with non SCA1 type OPCA]. 181 83

The patient, a 31-year-old married woman, noticed spasticity on walking at the age of 19 accompanied by ataxia, dysarthria and dysphagia. Facial twitching and dystonic movement of extremities have been observed since age 27. A sister of her father showed the similar ataxia and dysarthria, and expired of pneumonia at the age of 45. On admission at the age of 29, neurological examinations revealed nystagmus, marked spasticity with pathological reflexes and clonus, cerebellar ataxia, dysarthria and dysphagia, diffuse muscle wasting, fasciculation in facial musculature, and generalized slow dystonic movement. By neuro-otological studies bilateral MLF syndrome with upward gaze limitation and decreased velocity of saccadic eye movement were detected. Surface EMG at rest showed a dystonic discharges on the extremities. Needle EMG disclosed a systemic neurogenic change with reduced interference and high amplitude potentials. Atrophy of the brainstem was remarkable on the cranial CT and MRI. These abnormal eye movements, especially bilateral MLF syndrome and generalized dystonia seem to be quite unusual in the variety of spinocerebellar degenerations. On reviewing detected clinical descriptions on Joseph disease this case can be probably included.
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PMID:[A case of spinocerebellar degeneration with bilateral MLF syndrome and dystonia]. 274 81

Selective facial neurectomy in combination with bilateral musculocutaneous resection, plication brow lift, upper lid blepharoplasty, and limited rhytidectomy was performed on 18 patients with essential blepharospasm, eight with hemifacial spasm, and two with CNS vascular compression malformations. Microscopy showed the nerve tissues to be normal. Initial results were excellent. At 3 months there was a slight, persistent spastic twitching of the affected muscles in five nerves (a 14% failure rate in correcting blepharospasm). After 13 months there were four additional failures resulting from nerve regrowth in three and from one patient not completing therapy. The overall blepharospasm failure rate was 26%. On repeat neurectomy those with nerve regrowth presented with a diffuse, fine meshwork of nerve fibers reinnervating the mimetic facial musculature. In six of seven patients operated on again, spasticity was eliminated. The initial surgical failure rate has been corrected by resecting the frontal branch and the superior division of the buccal branch of the facial nerve. Only repeat neurectomy can correct long-term failures resulting from facial nerve regrowth.
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PMID:Selective facial neurectomy for spastic disorders of the facial nerve. 392 7

We studied a large pedigree with dominant spinocerebellar ataxia, genetically and clinically. At now, 27 members over 5 generations have been affected. Linkage study for the disease locus to D6S89 in a total of 44 individuals showed maximum lod scores of 3.99 at theta = 0.000. This result indicates that the disease locus of this pedigree locates near D6S89 on chromosome 6p (SCA 1). We studied 17 patients clinically. Mean age at onset was 37.7 +/- 8.6, and mean duration after onset was 11.3 +/- 6.8 years. Their clinical features were characterized by progressive ataxia, pyramidal involvement with hyperreflexia or spasticity, and mild posterior column involvement. Mild gaze nystagmus at early stage became unclear with the progress of illness. The frequent signs in the advanced stage were diffuse amyotropy, twitching of face or tongue, bulbar palsy, slow saccade, external ophthalmoparesis, mydriasis, coarse postural tremor, and dementia with emotional disturbance. There are so much clinical similarities between our pedigree and other SCA 1 pedigrees in the literature. Generally, SCA 1 shows hyperreflexia, spasticity, and terminal slow saccade. On the other hand, non-SCA 1 type OPCA is characterized by progressive hyporeflexia, slow eye movement from early stage, and frequent choreoathetosis. Gaze nystagmus, external ophthalmoparesis, amyotrophy, and spasticity are common in both SCA 1 and Machado-Joseph disease (MJD). However, they are more frequent in MJD than SCA 1. Moreover, extrapyramidal signs, such as dystonia, are rare is SCA 1. Based on these difference, SCA 1 could be clinically differentiated from other similar hereditary ataxias.
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PMID:[Spinocerebellar ataxia 1--clinical study of 17 patients in a large pedigree]. 836 44

In this case study, we describe the symptoms, neurological examination, and pathology of a woman with amyotrophic lateral sclerosis (ALS). ALS is a rare disorder leading to degeneration of the voluntary motor system and death in, on average, 3 to 4 years. The loss of motor neurons in the brain and spinal cord causes the progressive symptoms of muscular weakness, atrophy, fasciculation (muscle twitching), spasticity, and hyperreflexia. Signs of disease in both upper and lower motor neurons are required for a definitive clinical diagnosis. Pathology shows degeneration of the lateral corticospinal tracts, loss of motor neurons and astrogliosis in the brain and brain stem, and neuronal inclusions. This case was marked by the onset of weakness and muscle atrophy in the hand, which spread to involve contiguous muscle segments. Cognition, the extraocular muscles, and the urinary sphincters were spared. Respiratory muscle weakness was a late manifestation.
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PMID:Amyotrophic lateral sclerosis. 1295 82

Prostaglandin (PG) D2 is well known as a mediator of inflammation. Hematopoietic PGD synthase (HPGDS) is responsible for the production of PGD2 involved in inflammatory responses. Microglial activation and astrogliosis are commonly observed during neuroinflammation, including that which occurs during demyelination. Using the genetic demyelination mouse twitcher, a model of human Krabbe's disease, we discovered that activated microglia expressed HPGDS and activated astrocytes expressed the DP1 receptor for PGD2 in the brain of these mice. Cultured microglia actively produced PGD2 by the action of HPGDS. Cultured astrocytes expressed two types of PGD2 receptor, DP1 and DP2, and showed enhanced GFAP production after stimulation of either receptor with its respective agonist. These results suggest that PGD2 plays an important role in microglia/astrocyte interaction. We demonstrated that the blockade of the HPGDS/PGD2/DP signaling pathway using HPGDS- or DP1-null twitcher mice, and twitcher mice treated with an HPGDS inhibitor, HQL-79 (4-benzhydryloxy-1-[3-(1H-tetrazol-5-yl)-propyl]piperidine), resulted in remarkable suppression of astrogliosis and demyelination, as well as a reduction in twitching and spasticity. Furthermore, we found that the degree of oligodendroglial apoptosis was also reduced in HPGDS-null and HQL-79-treated twitcher mice. These results suggest that PGD2 is the key neuroinflammatory molecule that heightens the pathological response to demyelination in twitcher mice.
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PMID:Prostaglandin D2-mediated microglia/astrocyte interaction enhances astrogliosis and demyelination in twitcher. 1662 58

Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurological disease that affects approximately 20,000 Americans. Symptoms include muscle weakness, fatigue, twitching, atrophy, spasticity, pain, oropharyngeal dysfunction, pseudobulbar affect, weight loss, and respiratory impairment. Death occurs within 3-5 yr after onset of symptoms, with diagnosis taking from 11 to 17.5 months. The only FDA-approved drug for ALS is Riluzole, which only increases the life expectancy by a few months. All other treatments for ALS provide symptom management to improve the patient's quality of life. An interdisciplinary palliative care team for the ALS patient helps to reduce the stress that the illness places on families. Massage can be a useful adjunctive treatment for spasticity and pain when medication side effects are unwanted. A holistic interdisciplinary palliative care team supports both the patient and the family improving their quality of life.
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PMID:Interdisciplinary palliative care, including massage, in treatment of amyotrophic lateral sclerosis. 1976 55

Miles-Carpenter syndrome (MCS) was described in 1991 as an XLID syndrome with fingertip arches and contractures and mapped to proximal Xq. Patients had microcephaly, short stature, mild spasticity, thoracic scoliosis, hyperextendable MCP joints, rocker-bottom feet, hyperextended elbows and knees. A mutation, p.L66H, in ZC4H2, was identified in a XLID re-sequencing project. Additional screening of linked families and next generation sequencing of XLID families identified three ZC4H2 mutations: p.R18K, p.R213W and p.V75in15aa. The families shared some relevant clinical features. In silico modeling of the mutant proteins indicated all alterations would destabilize the protein. Knockout mutations in zc4h2 were created in zebrafish and homozygous mutant larvae exhibited abnormal swimming, increased twitching, defective eye movement and pectoral fin contractures. Because several of the behavioral defects were consistent with hyperactivity, we examined the underlying neuronal defects and found that sensory neurons and motoneurons appeared normal. However, we observed a striking reduction in GABAergic interneurons. Analysis of cell-type-specific markers showed a specific loss of V2 interneurons in the brain and spinal cord, likely arising from mis-specification of neural progenitors. Injected human wt ZC4H2 rescued the mutant phenotype. Mutant zebrafish injected with human p.L66H or p.R213W mRNA failed to be rescued, while the p.R18K mRNA was able to rescue the interneuron defect. Our findings clearly support ZC4H2 as a novel XLID gene with a required function in interneuron development. Loss of function of ZC4H2 thus likely results in altered connectivity of many brain and spinal circuits.
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PMID:ZC4H2, an XLID gene, is required for the generation of a specific subset of CNS interneurons. 2605 27